Se revisan los géneros de chinches de encaje (Tingidae) del Nuevo Mundo pertenecientes al complej... more Se revisan los géneros de chinches de encaje (Tingidae) del Nuevo Mundo pertenecientes al complejo Tigava. Se describen dos nuevos géneros y especies Mexicotingis brailovskyi de México, y Paraceratotingis convergens, de Venezuela. Se brindan diagnosis, descripciones, y fotos en color de los nuevos taxa, diagnosis y fotografías de la cabeza y el pronoto de todos los géneros, una lista actualizada de las distribuciones de todas sus especies, y una clave para géneros para distinguir estos Tingidae estrechamente emparentados.The lace bug (Tingidae) genera belonging to the New World Tigava complex are reviewed. The two new genera and new species Mexicotingis brailovskyi, from México, and Paraceratotingis convergens, from Venezuela, are described. Diagnoses, descriptions, and digital color photographs of the new taxa, diagnoses and digital photographs of the heads and pronota of all genera, an updated checklist and distributions of the included species, and a key to genera are provided to...
It was concluded that Paederus littoralis (L) is homogeneously distributed throughout the selecte... more It was concluded that Paederus littoralis (L) is homogeneously distributed throughout the selected area. Studies on Paederus spp. was started in March, 2007 and continued till October, 2008. Over 8,000 specimens were collected from the different parts of District Thatta, Sindh, Pakistan. Food preference of rove beetles was studied under laboratory conditions. Aphids 95-99% in A&C. Batch whereas all aphids (50) in Batch B. Studies revealed that adults were often very active, always preferring to eat natural diet regardless of the presence of artificial diets.
The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defences against ... more The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defences against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identified etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step-2 activators. High concentrations of these metabolites fully and rapidly activated pyrin, in a human-specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases (PAAND and FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, displayed increased responses to these metabolites. This study provides a new perspective on pyrin activation, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and expl...
ABSTRACTGuanylate-Binding Proteins (GBPs) are interferon-inducible GTPases that play a key role i... more ABSTRACTGuanylate-Binding Proteins (GBPs) are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Seven GBPs are present in humans. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key step for the antimicrobial activity of GBPs towards cytosolic bacteria is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are formed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2, 3, and 4.Here, we investigated GBPs recruitment on Francisella novicida, a professional cytosol-dwelling pathogen with an atypical tetra-acylated LPS. Co-infection experiments demonstrated that GBPs target preferentially S. flexneri compared to F. novicida. F. novicida was coated by GBP1 and GBP2 in human macrophages but escaped targeting by GBP3 and GBP4. GBP1 and GBP2 features...
Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their acti... more Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their activity is tightly regulated at the transcriptional and post-transcriptional levels. In this review, we present the transcriptional regulation of inflammasome genes from sensors (e.g NLRP3) to substrates (e.g. IL-1β). Lineage-determining transcription factors shape inflammasome responses in different cell types with profound consequences on the responsiveness to inflammasome-activating stimuli. Pro-inflammatory signals (sterile or microbial) have a key transcriptional impact on inflammasome genes, which is largely mediated by NF-κB and, that translates into higher antimicrobial immune responses. Furthermore, diverse intrinsic (e.g. circadian clock, metabolites) or extrinsic (e.g. xenobiotics) signals are integrated by signal-dependent transcription factors and chromatin structure changes to modulate transcriptionally inflammasome responses. Finally, anti-inflammatory signals (e.g. IL-10) co...
Caspase‐4, the cytosolic LPS sensor, and gasdermin D, its downstream effector, constitute the non... more Caspase‐4, the cytosolic LPS sensor, and gasdermin D, its downstream effector, constitute the non‐canonical inflammasome, which drives inflammatory responses during Gram‐negative bacterial infections. It remains unclear whether other proteins regulate cytosolic LPS sensing, particularly in human cells. Here, we conduct a genome‐wide CRISPR/Cas9 screen in a human monocyte cell line to identify genes controlling cytosolic LPS‐mediated pyroptosis. We find that the transcription factor, IRF2, is required for pyroptosis following cytosolic LPS delivery and functions by directly regulating caspase‐4 levels in human monocytes and iPSC‐derived monocytes. CASP4, GSDMD, and IRF2 are the only genes identified with high significance in this screen highlighting the simplicity of the non‐canonical inflammasome. Upon IFN‐γ priming, IRF1 induction compensates IRF2 deficiency, leading to robust caspase‐4 expression. Deficiency in IRF2 results in dampened inflammasome responses upon infection with Gram‐negative bacteria. This study emphasizes the central role of IRF family members as specific regulators of the non‐canonical inflammasome.
Nine new species of jumping tree bugs, or Isometopinae, from Argentina, Paraguay, and southern Br... more Nine new species of jumping tree bugs, or Isometopinae, from Argentina, Paraguay, and southern Brazil are described. The genus Aristotelesia is revised and the two new species A. fuscata (from Brazil) and A. medialis (from Argentina) are described, and the Argentine and Paraguayan species of Myiomma are reviewed and the seven new species M. apicalis (from Paraguay), M. argentinensis (from Argentina and Paraguay), M. binotata (from Argentina), M. pallidopleura (from Argentina), M. pallipes (from Argentina), M. scutellata (from Paraguay), and M. uniformis (from Argentina) are described. Previously published records of isometopines from Argentina are clarified. Color photographs, illustrations of the parameres of M. argentinensis, and keys are provided to help distinguish species.
Congress created the tropical disease priority review voucher program to stimulate new drug devel... more Congress created the tropical disease priority review voucher program to stimulate new drug development for tropical diseases. An analysis of the pharmaceutical pipeline indicates that the development of drugs for these tropical diseases has increased. However, the effects of the program are not uniform across all diseases, as malaria and tuberculosis have seen significant new drug development, while other diseases have not.
The inflammasome is a major component of the innate immune system, and its main function is to ac... more The inflammasome is a major component of the innate immune system, and its main function is to activate caspase-1, a cysteine protease that promotes inflammation by inducing interleukin-1β (IL-1β) maturation and release into the extracellular milieu. To prevent uncontrolled inflammation, this complex is highly regulated. Once it is assembled, the inflammasome is insoluble, which has long precluded the analysis of its interactions with other proteins. Here, we used the proximity-dependent biotinylation assay (BioID) to identify proteins associated with caspase-1 during inflammasome activation. Using the BioID in a cell-free system in which the inflammasome had been activated, we found that a caspase-1-biotin ligase fusion protein selectively labeled 111 candidates, including the p62/sequestosome-1 protein (p62). Using co-immunoprecipitation experiments, we demonstrated that p62 interacts with caspase-1. This interaction promoted caspase-1-mediated cleavage of p62 at Asp-329. Mechanis...
The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB... more The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1 mice. Compared to humans, murine hC5aR1 neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1 mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonst...
Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipo... more Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our results indicate functional differences between human caspase-4 and murine caspase-11. We further establish that human Guanylate-binding proteins promote inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a broader reactivity of caspase-4 to under-acylated LPS than ca...
Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsi... more Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes co...
Se revisan los géneros de chinches de encaje (Tingidae) del Nuevo Mundo pertenecientes al complej... more Se revisan los géneros de chinches de encaje (Tingidae) del Nuevo Mundo pertenecientes al complejo Tigava. Se describen dos nuevos géneros y especies Mexicotingis brailovskyi de México, y Paraceratotingis convergens, de Venezuela. Se brindan diagnosis, descripciones, y fotos en color de los nuevos taxa, diagnosis y fotografías de la cabeza y el pronoto de todos los géneros, una lista actualizada de las distribuciones de todas sus especies, y una clave para géneros para distinguir estos Tingidae estrechamente emparentados.The lace bug (Tingidae) genera belonging to the New World Tigava complex are reviewed. The two new genera and new species Mexicotingis brailovskyi, from México, and Paraceratotingis convergens, from Venezuela, are described. Diagnoses, descriptions, and digital color photographs of the new taxa, diagnoses and digital photographs of the heads and pronota of all genera, an updated checklist and distributions of the included species, and a key to genera are provided to...
It was concluded that Paederus littoralis (L) is homogeneously distributed throughout the selecte... more It was concluded that Paederus littoralis (L) is homogeneously distributed throughout the selected area. Studies on Paederus spp. was started in March, 2007 and continued till October, 2008. Over 8,000 specimens were collected from the different parts of District Thatta, Sindh, Pakistan. Food preference of rove beetles was studied under laboratory conditions. Aphids 95-99% in A&C. Batch whereas all aphids (50) in Batch B. Studies revealed that adults were often very active, always preferring to eat natural diet regardless of the presence of artificial diets.
The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defences against ... more The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defences against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identified etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step-2 activators. High concentrations of these metabolites fully and rapidly activated pyrin, in a human-specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases (PAAND and FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, displayed increased responses to these metabolites. This study provides a new perspective on pyrin activation, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and expl...
ABSTRACTGuanylate-Binding Proteins (GBPs) are interferon-inducible GTPases that play a key role i... more ABSTRACTGuanylate-Binding Proteins (GBPs) are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Seven GBPs are present in humans. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key step for the antimicrobial activity of GBPs towards cytosolic bacteria is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are formed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2, 3, and 4.Here, we investigated GBPs recruitment on Francisella novicida, a professional cytosol-dwelling pathogen with an atypical tetra-acylated LPS. Co-infection experiments demonstrated that GBPs target preferentially S. flexneri compared to F. novicida. F. novicida was coated by GBP1 and GBP2 in human macrophages but escaped targeting by GBP3 and GBP4. GBP1 and GBP2 features...
Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their acti... more Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their activity is tightly regulated at the transcriptional and post-transcriptional levels. In this review, we present the transcriptional regulation of inflammasome genes from sensors (e.g NLRP3) to substrates (e.g. IL-1β). Lineage-determining transcription factors shape inflammasome responses in different cell types with profound consequences on the responsiveness to inflammasome-activating stimuli. Pro-inflammatory signals (sterile or microbial) have a key transcriptional impact on inflammasome genes, which is largely mediated by NF-κB and, that translates into higher antimicrobial immune responses. Furthermore, diverse intrinsic (e.g. circadian clock, metabolites) or extrinsic (e.g. xenobiotics) signals are integrated by signal-dependent transcription factors and chromatin structure changes to modulate transcriptionally inflammasome responses. Finally, anti-inflammatory signals (e.g. IL-10) co...
Caspase‐4, the cytosolic LPS sensor, and gasdermin D, its downstream effector, constitute the non... more Caspase‐4, the cytosolic LPS sensor, and gasdermin D, its downstream effector, constitute the non‐canonical inflammasome, which drives inflammatory responses during Gram‐negative bacterial infections. It remains unclear whether other proteins regulate cytosolic LPS sensing, particularly in human cells. Here, we conduct a genome‐wide CRISPR/Cas9 screen in a human monocyte cell line to identify genes controlling cytosolic LPS‐mediated pyroptosis. We find that the transcription factor, IRF2, is required for pyroptosis following cytosolic LPS delivery and functions by directly regulating caspase‐4 levels in human monocytes and iPSC‐derived monocytes. CASP4, GSDMD, and IRF2 are the only genes identified with high significance in this screen highlighting the simplicity of the non‐canonical inflammasome. Upon IFN‐γ priming, IRF1 induction compensates IRF2 deficiency, leading to robust caspase‐4 expression. Deficiency in IRF2 results in dampened inflammasome responses upon infection with Gram‐negative bacteria. This study emphasizes the central role of IRF family members as specific regulators of the non‐canonical inflammasome.
Nine new species of jumping tree bugs, or Isometopinae, from Argentina, Paraguay, and southern Br... more Nine new species of jumping tree bugs, or Isometopinae, from Argentina, Paraguay, and southern Brazil are described. The genus Aristotelesia is revised and the two new species A. fuscata (from Brazil) and A. medialis (from Argentina) are described, and the Argentine and Paraguayan species of Myiomma are reviewed and the seven new species M. apicalis (from Paraguay), M. argentinensis (from Argentina and Paraguay), M. binotata (from Argentina), M. pallidopleura (from Argentina), M. pallipes (from Argentina), M. scutellata (from Paraguay), and M. uniformis (from Argentina) are described. Previously published records of isometopines from Argentina are clarified. Color photographs, illustrations of the parameres of M. argentinensis, and keys are provided to help distinguish species.
Congress created the tropical disease priority review voucher program to stimulate new drug devel... more Congress created the tropical disease priority review voucher program to stimulate new drug development for tropical diseases. An analysis of the pharmaceutical pipeline indicates that the development of drugs for these tropical diseases has increased. However, the effects of the program are not uniform across all diseases, as malaria and tuberculosis have seen significant new drug development, while other diseases have not.
The inflammasome is a major component of the innate immune system, and its main function is to ac... more The inflammasome is a major component of the innate immune system, and its main function is to activate caspase-1, a cysteine protease that promotes inflammation by inducing interleukin-1β (IL-1β) maturation and release into the extracellular milieu. To prevent uncontrolled inflammation, this complex is highly regulated. Once it is assembled, the inflammasome is insoluble, which has long precluded the analysis of its interactions with other proteins. Here, we used the proximity-dependent biotinylation assay (BioID) to identify proteins associated with caspase-1 during inflammasome activation. Using the BioID in a cell-free system in which the inflammasome had been activated, we found that a caspase-1-biotin ligase fusion protein selectively labeled 111 candidates, including the p62/sequestosome-1 protein (p62). Using co-immunoprecipitation experiments, we demonstrated that p62 interacts with caspase-1. This interaction promoted caspase-1-mediated cleavage of p62 at Asp-329. Mechanis...
The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB... more The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1 mice. Compared to humans, murine hC5aR1 neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1 mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonst...
Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipo... more Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our results indicate functional differences between human caspase-4 and murine caspase-11. We further establish that human Guanylate-binding proteins promote inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a broader reactivity of caspase-4 to under-acylated LPS than ca...
Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsi... more Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes co...
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Papers by Thomas Henry